Heterocyclic compounds as triggering receptor expressed on myeloid cells 2 agonists and methods of use

Abstract

The present disclosure provides compounds of Formula I, useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 (“TREM2”). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a neurodegenerative disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula I.

What is claimed is: 
     
       1. A method of treating Parkinson's disease, rheumatoid arthritis, Alzheimer's disease, Nasu-Hakola disease, frontotemporal dementia, multiple sclerosis, prion disease, or stroke in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       2. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       3. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       4. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       5. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       6. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       7. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       8. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       9. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       10. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       11. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       12. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       13. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       14. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       15. The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       16. The method of  claim 1 , wherein the disease or condition is Alzheimer's disease. 
     
     
       17. The method of  claim 1 , wherein the disease or condition is Nasu-Hakola disease. 
     
     
       18. The method of  claim 1 , wherein the compound or tautomer thereof, or pharmaceutically acceptable salt of said compound or said tautomer is administered as a pharmaceutical composition comprising a pharmaceutically acceptable excipient and the compound or tautomer thereof, or pharmaceutically acceptable salt of said compound or said tautomer. 
     
     
       19. The method of  claim 1 , wherein the pharmaceutical composition is administered orally, mucosally, topically, transdermally, rectally, pulmonarily, parentally, intranasally, intravascularly, intravenously, intraarterial, intraperitoneally, intrathecally, subcutaneously, sublingually, intramuscularly, intrasternally, vaginally, or by infusion techniques. 
     
     
       20. The method of  claim 19 , wherein the pharmaceutical composition is orally administered.